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Biomedical subjects

S Saji

Publications and source records attributed to S Saji.

At least 91 records · Page 5Linked to original sources
PubMed1996

Prognostic value of preoperative immunosuppressive acidic protein in patients with gastric carcinoma. Findings from three independent clinical trials. Tumor Marker Committee for the Study Group of Immunochemotherapy with PSK for Gastric Cancer.

BACKGROUND: Immunosuppressive acidic protein (IAP) has been reported to have close correlation with the impairment of host immune response. To evaluate the significance of IAP in clinical studies, the prognostic value of preoperative IAP was investigated in clinical trials of patients with gastric carcinoma after curative resection. METHODS: An appropriate IAP threshold value of 580 micrograms/mL was determined using Cox's proportional hazards model. Five-year survival rates were estimated for high and low IAP groups in three different clinical studies. Meta-analysis was performed based on individual patient data, and summarized hazard ratios were estimated using a stratified proportional hazards model. RESULTS: Meta-analysis of the three clinical trials demonstrated that patients with preoperative IAP levels above the threshold had significantly poorer cancer related survival (P = 0.0039) and absolute survival (P = 0.0023), even after adjustment for the major prognostic factors. CONCLUSIONS: Gastric carcinoma patients with an IAP value above the threshold level of 580 micrograms/mL have a higher risk of cancer death and absolute death than patients with an IAP value below the threshold value.

Adult↗
PubMed1996

Somatic alterations of the DPC4 gene in human colorectal cancers in vivo.

BACKGROUND & AIMS: The chromosome region 18q21 has been shown to be frequently deleted in colorectal cancers, and such frequent allelic loss is a hallmark of the presence of a tumor-suppressor gene. The DPC4 gene, which is located at 18q21, has been identified as a tumor-suppressor gene from examination of pancreatic cancers. The aim of the present study was to determine if it might also be altered in colorectal cancers. METHODS: Mutation analyses of the DPC4 gene were performed on complementary DNA samples from 31 primary colorectal cancer specimens using a combination of polymerase chain reaction, single-strand conformation polymorphism, and DNA sequencing. RESULTS: Four missense mutations producing amino acid substitutions and a somatic 12-base pair deletion in the coding region of the DPC4 gene were detected in the 31 cancers (16%; 5 of 31). CONCLUSIONS: The DPC4 gene may play a role as a tumor-suppressor gene in a fraction of colorectal cancers; however, while allelic loss at 18q21 is very often seen in colorectal cancers, only a minority show DPC4 mutations, suggesting that there might be another tumor-suppressor gene in this chromosome region.

Adult↗
PubMed1996

Mitogen-activated protein kinase activation in hepatocyte growth factor-stimulated rat hepatocytes: involvement of protein tyrosine kinase and protein kinase C.

Hepatocyte growth factor (HGF) stimulated mitogen-activated protein (MAP) kinases and MAP kinase kinase in primary cultured rat hepatocytes. Inhibitors for protein kinase C (PKC), Ro31-8425, H-7, and calphostin C, reduced HGF-induced MAP kinase activity. A PKC activator, phorbol myristate acetate (PMA), induced MAP kinase activation in a concentration-dependent manner. Protein tyrosine kinase (PTK) inhibitors, genistein, and ST638 also inhibited HGF-induced MAP kinase activation. Furthermore, HGF increased formation of Ras guanosine triphosphate (GTP) complex, indicating Ras activation. Genistein inhibited HGF-induced Ras activation, but Ro31-8425 was without effect. On the other hand, Ro31-8425 decreased HGF-induced [3H]arachidonic acid (AA) release and [3H]thymidine incorporation. Genistein also prevented [3H]AA release and [3H]-thymidine incorporation. Moreover, a commonly used phospholipase A2 (PLA2) inhibitor, quinacrine, decreased HGF-induced [3H]AA release and [3H]thymidine incorporation. The inhibitory profile of [3H]AA release was well correlated with that of [3H]thymidine incorporation in Ro31-8425-, genistein-, and quinacrine-treated cells. A cyclooxygenase inhibitor, indomethacin, which suppressed HGF-induced DNA synthesis, had minimal effect on MAP kinase activation. In contrast, prostaglandin (PG) E1, E2, or F2 alpha, which stimulate [3H]thymidine incorporation to the same level as that caused by HGF in hepatocytes, caused very weak activation of MAP kinases. These results suggest that PTK, Ras, and PKC play roles in MAP kinase activation induced by HGF and that MAP kinase activation resulting in AA release is involved in DNA synthesis in rat hepatocytes.

Animals↗
PubMed1996

Phospholipase D activation in hepatocyte growth factor-stimulated rat hepatocytes mediates the expressions of c-jun and c-fos: involvement of protein tyrosine kinase, protein kinase C, and Ca2+.

Hepatocyte growth factor (HGF) activated phospholipase D (PLD) in primary-cultured rat hepatocytes, as assessed by the formation of phosphatidylbutanol (PBut), a specific and stable product of PLD activity in the presence of 0.3% butanol. PLD hydrolyzes phosphatidylcholine to choline and phosphatidic acid (PA), which is further metabolized to diacylglycerol (DG) by PA phosphohydrolase (PAP). In HGF-stimulated hepatocytes, butanol prevented the formation of PA and DG. A PAP inhibitor, propranolol, inhibited DG production with a reciprocal increase of PA, implying that PLD played a role in the formation of not only PA but DG. Inhibitors for protein kinase C (PKC), Ro31-8425, H-7, and calphostin C, reduced HGF-induced PLD activation. A protein tyrosine kinase (PTK) inhibitor, genistein but not its inactive analogue daidzein, inhibited PLD activation by HGF. Moreover, depletion of extracellular Ca2+ by omission of Ca2+ or by chelating residual Ca2+ with ethyleneglycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) abolished HGF-induced PLD activation. HGF, phorbol myristate acetate (PMA) and a DG analog, oleylacetylglycerol (OAG), activated the expression of c-jun and c-fos messenger RNAs (mRNAs). Ro31-8425, calphostin C, and genistein, which prevented HGF-induced PLD activation, inhibited induction of these immediate early genes. Butanol and propranolol at concentrations which effectively inhibited the formation of DG, suppressed HGF-induced expression of c-jun and c-fos mRNAs. However, HGF-induced mitogen-activated protein kinase (MAPK) activation was not affected by both butanol and propranolol. These results suggest that PTK, PKC, and Ca2+ regulate HGF-induced PLD activation, and that DG produced by PLD pathway may play a role in the induction of immediate early genes, which is activated in MAPK-independent manner, in rat hepatocytes.

Animals↗
PubMed1996

Palliative therapy using polyurethane-covered self-expandable metallic stents for malignant esophageal strictures: experiences in six patients.

To evaluate the utility and limitations of palliative stenting with polyurethane-covered self-expandable metallic stents, 6 patients (3 males and 3 females ranging in age from 58-85 [mean 72.1] years) with malignant esophageal strictures were treated with these stents between April 1993 and October 1995. Three had esophageal carcinoma, two had gastric carcinoma and one had lung carcinoma. Song-type self-expandable metallic stents were inserted by intubation under local laryngeal anesthesia. A retriever was attached in 4 stents and an anti-reflux mechanism was attached in 2 stents placed over the esophagocardiac strictures. The stents were placed successfully in all patients, and no major complication related to intubation was encountered. All the stents fully expanded within 3 days after insertion. The grade of dysphagia was improved in 5 (83%) of the 6 patients. One stent was extracted using a retriever in one patient with no improvement. No reflux symptoms were observed in 2 patients whom received stents with an anti-reflux mechanism. No blockage of the stent due to food impaction or secondary stricture occurred in any patient during the observation period. One stent migrated into the stomach in one patient 27 days after insertion. Esophageal stenting with polyurethane-covered self-expandable metallic stents is a relatively safe and effective palliation for malignant esophageal strictures.

Aged↗
PubMed1996

[Distributions of pyrimidine nucleoside phosphorylase (PyNPase) in tissues of benign and malignant mammary diseases--immunohistochemical observations].

Pyrimidine nucleoside phosphorylase (PyNPase) is considered to be important for producing antitumor function of 5'-DFUR or 5-FU inducing compounds, since this enzyme transforms 5'-DFUR into 5-FU and 5-FU into their activated forms. Additionally, PyNPase shows high activity in various malignant tumor tissues. In this investigation, the distributions of PyNPase were examined in the tissues of mastopathy, fibroadenoma, phyllodes tumor and mammary cancer using immunohistochemical procedures. The following results were obtained. In the tissues of mastopathy or fibroadenoma, immunoreactivity was generally very weak and only a few positive epithelial cells were observed. In the phyllodes tumor, immunoreactivity was also weak, but every epithelial cell showed positive immunoreactivity. On the contrary, apparent immunoreactivity was observed in the tissues of mammary cancer, and cancer cells revealed prominent immunoreactivity.

Breast↗
PubMed1996

Regulation of endothelial growth factor expressions in breast cancer.

Expression of various endothelial growth factors including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), Platelet-derived endothelial cell growth factor (PD-ECGF) and hepatocyte growth factor (HGF) was investigated in human breast carcinoma tissues, and the results were compared to the intratumoral microvessel density evaluated by the immunostaining to anti-factor VIII related antigen. VEGF and PD-ECGF were examined by immunostainings, and bFGF and HGF were assessed by enzymatic immunoassays. As a result, VEGF and PD-ECGF were significantly associated with the increment of microvessel density, although no significant correlation was found with bFGF and HGF. In addition, interestingly, a tendency of co-expression between VEGF and PD-ECGF was demonstrated. It was suggested that VEGF and PD-ECGF play important roles in the promotion of angiogenesis in human breast cancer.

Breast Neoplasms↗
PubMed1996

[The importance of tumor angiogenesis as a prognostic indicator in primary breast cancer].

Recently, the importance of tumor angiogenesis in the process of tumor growth, progression and metastasis in solid tumors has been widely accepted. The prognostic value of angiogenesis has been demonstrated in a variety of solid tumors including breast cancer. In this report, we reviewed recent studies investigating on the value of intratumoral microvessel density (MVD), assessed by a sermiquantitative immunohistochemical assay with using factor-VIII related antibody or anti CD-31 antibody, as a prognostic indicator in primary breast cancer patients. Studies using factor-VIII related antibody showed that the average MVD ranged from 67.3 to 84.0 counts per mm2 area. When used by anti CD-31 monoclonal antibody, the average MVD were 120.3 approximately 135 counts per mm2 area in the range. More than 8 clinical investigations have showed that MVD was a potent prognostic indicator for relapse free survival and/or overall survival in both node-negative and -positive patients. Two reports concluded no prognostic value of MVD, however the average MVD of these two studies significantly differed from other reports. Thus, at present, angiogenesis grade seems to provide an independent prognostic value when the MVD was properly assessed. With respect to the relationship with conventional prognostic indicators, several reports showed the tendency that increased MVD was correlated with younger age and increase of tumor size below 3 cm diameter, however, some reports failed to demonstrate the tendency, suggesting that these correlations are still in controversial. Biological markers including ER, p53 and c-erB2 showed no correlation with the MVD in many studies including our investigation. Only a significant correlation we found was that MVD was increased in tumors with the expression of vascular endothelial growth factor and platelet-derived endothelial cell growth factor, which are noted to be potent endothelial growth factor. Since the evaluation of tumor angiogenesis as a prognostic indicator is now widely investigated in a prospective study, MVD might be introduced to the category of the criteria for determining the schedule of postoperative adjuvant therapy of breast cancer.

Age Factors↗
PubMed1996

A case of strangulated transomental hernia diagnosed preoperatively.

A patient with an unusual case of internal hernia was treated successfully with surgery for strangulated transomental hernia, diagnosed preoperatively by abdominal computed tomographic examination (CT). The herniation occurred through congenital defects in the gastrocolic omentum. Herniation of this nature is extremely rare, and abdominal CT examination is very useful for preoperative diagnosis.

Adult↗
PubMed1996

[Locoregional therapy for liver metastases of colorectal cancer].

The role of biological response modifiers (BRM) in locoregional therapy for liver metastases of colorectal cancer was studied clinically and experimentally. Seven patients with numerous metastases to both lobes of liver were given intraarterial administration of BRM in combination with anticancer drugs. A partial response was observed in 1 patient. The response rate was 14.3%. Alternatively, intraarterial administration of both OK-432 and IL-2 into the rabbit with liver metastases of VX-2 tumors could bring about the infiltration of cytotoxic T lymphocytes around the tumors, followed by a significant decrease of the metastatic nodules. In addition, the same anti-tumor effect was observed when PSK was administered intraperitoneally into the BALB/c mouse with liver metastases of colon 26 tumors. Moreover, the therapeutic effect of water in oil type emulsion encapsulating both OK-432 and IL-2 was greater than that of the solution of BRM in BALB/c mouse with liver metastases of colon 26 tumors. These results indicated that BRM could be one of the promising agents in locoregional therapy against liver metastases of colorectal cancer.

Adult↗
PubMed1995

Distinct mutational spectrum of the p53 gene in lung cancers from Chinese women in Hong Kong.

Accumulating evidence suggests that the p53 gene is a good target for molecular epidemiological studies to search for risk factors in carcinogenic events. The lung cancer incidence for females in Hong Kong is unusually high, ranking among the highest in the world despite a low percentage with a history of smoking. To gain insights into possible etiological risk factors responsible for this high incidence, we examined p53 mutations in 35 lung cancer specimens from Chinese females living in Hong Kong and compared them with 35 matched cases from Japanese women as well as previously reported p53 mutations in the world literature. p53 mutations in exons 5-8 were present in 20 and 31% of the Hong Kong and Japanese cases, respectively. Notably, single-base deletions within runs of identical bases were observed in 3 (43%) of the 7 mutations in the Hong Kong cases, in contrast to the absence of such mutations in the controls and the extreme scarcity in the literature, suggesting that distinct environmental and/or genetic factor(s) might be involved. Although the frequent occurrence of characteristic single-base deletions could be a reflection of mutator mutations leading to inefficient mismatch repair of slipped strand mispairings, none of the lung cancer specimens exhibited such microsatellite instabilities.

Adult↗
PubMed1995

Utility of Tc-99m GSA SPECT imaging in estimation of functional volume of liver segments in health and liver diseases.

The authors examined whether there was a difference in liver function among hepatic segments in liver cirrhosis cases, and in cases of hepatocellular carcinoma (HCC) associated with liver cirrhosis. If the average counts in the lateral segment of the left lobe were set at 1, the average counts in the right upper and lower segment of the liver were 0.75 approximately 1.02 (0.89 +/- 0.09, mean +/- SD) in normal cases, 0.38 approximately 2.24 (1.01 +/- 0.39) in liver cirrhosis cases, and 0.61 approximately 2.85 (1.15 +/- 0.58) in HCC cases. There is a significant difference between normal cases and liver cirrhosis cases or HCC cases (P < 0.001). Also, in HCC cases, if the average counts in the cancer-bearing segment of the liver were set at 1, the average counts in the noncancerous segment of the liver were 0.55 approximately 2.85 (1.23 +/- 0.58), and many average counts in the cancer-bearing segment were equal to, or lower than those in the noncancerous segment. It has been found that there were significant differences in function among hepatic segments in liver cirrhosis cases, and in HCC cases. Furthermore, the liver function in the cancer-bearing segment tended to be worse due to the existence of carcinoma compared with that in the noncancerous segment.

Adult↗
PubMed1995

Roles of prostaglandin production and mitogen-activated protein kinase activation in hepatocyte growth factor-mediated rat hepatocyte proliferation.

Hepatocyte growth factor (HGF) and epidermal growth factor (EGF)-stimulated DNA synthesis in primary cultured rat hepatocytes. HGF-induced DNA synthesis was concentration-dependently inhibited by a cyclooxygenase inhibitor, indomethacin. BW755C, a dual inhibitor for cyclooxygenase and lipoxygenase activities, also inhibited hepatocyte growth. Prostaglandin E1 (PGE1), PGE2, and PGF2 alpha induced DNA synthesis even at such a low concentration as 5 nmol/L and potentiated [3H]thymidine incorporation induced by HGF in an additive manner. HGF caused arachidonic acid (AA) release and eicosanoid production. These events were detectable within 10 minutes after stimulation and lasted for at least 60 minutes. Furthermore, two proteins with approximately 40 kd were tyrosine phosphorylated by HGF. These proteins were identified as p42/p44 mitogen-activated protein (MAP) kinases by anti-MAP kinase immunoblots, which were known to activate cytosolic phospholipase A2 (cPLA2), a key enzyme in AA release. Activation of MAP kinases was detectable within 5 minutes after stimulation with HGF and lasted for at least 60 minutes. EGF-mediated DNA synthesis was also inhibited by the above cyclooxygenase inhibitors. EGF caused AA release and tyrosine phosphorylation of MAP kinases. These results suggest that HGF as well as EGF causes AA release, probably through activation of cPLA2 mediated by MAP kinases, and that PGs, metabolites of AA, might play a pivotal role in hepatocyte proliferation in an autocrine mechanism.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1995

[A new modality of locoregional chemotherapy based on biochemical double modulation of 5-fluorouracil with both leucovorin and cisplatin against liver metastases of colorectal cancer].

A new modality of locoregional chemotherapy based on biochemical double modulation of 5-fluorouracil (FU) with both leucovorin (LV) and cisplatin (CDDP) against liver metastases of colorectal cancer was devised. The schedule for the locoregional therapy was as follows; bolus infusion of LV (6 mg/body) followed by 30-minute infusion of CDDP (10 mg/body) and 30-minute infusion of 5-FU (250 mg/body). Four colorectal cancer patients with numerous metastases to both lobes of liver were given intraarterial administration of above anticancer drugs every 1-2 weeks after resection of primary lesions. On the one hand, 3 colorectal cancer patients, who developed a few metastases to both lobes of liver, were treated preventively by the same schedule every 2-3 weeks after the resection of metastatic tumors. As for the clinical (radiographic) response, complete response and partial response were observed in 1 and 2 of 4 patients, respectively. The response rate was 75%. No new lesions appeared for over 1 year by the preventive treatment in 2 of 3 patients, whereas new lesions appeared in one patient at 3 months after discontinuation of treatment because of mild toxicity. The toxicity, however, was within acceptable limits. These results indicated that biochemical double modulation of 5-FU with both LV and CDDP is a very promising locoregional chemotherapy against liver metastases of colorectal cancer.

Aged↗
PubMed1995

[A study on the relationship between clinicopathological findings of gastric cancer and its biological behavior such as DNA ploidy pattern and immunohistochemical staining of PCNA, laminin, p53 and nm 23].

UNLABELLED: The quantity of DNA ploidy and the expression of PCNA, laminin, p53 and nm23 by immunohistochemical stain were investigated using paraffin-embedded specimens obtained from 135 gastric cancer patients, and were compared with clinicopathological findings. RESULTS: (1) The incidence of DNA high ploidy (HP) was significantly higher in such a case with infiltrating type (INF) and positive lymph node metastasis (p+) compared with that of negative cases. (2) The high level of PCNA labeling index (HLI), negative expression of laminin (NEL) and nm23 (NE23) were more frequently observed in INF; large tumor size, deep invasion and p+, while positive p 53 was noted only in p+ cases. (3) The survival curve of HP, HLI, NEL, and NE 23 was significantly lower than that of the cases showing the reverse findings. As a conclusion, it is suggested that the investigation of the DNA ploidy, PCNA, laminin, p53 and nm23 might be useful as a parameter of biological behavior for gastric cancer and the prognosis of gastrectomized patients.

DNA, Neoplasm↗
PubMed1994

Efficacy of immunochemotherapy as adjuvant treatment after curative resection of gastric cancer. Study Group of Immunochemotherapy with PSK for Gastric Cancer.

In Japan the standard adjuvant treatment after resection of gastric cancer is intravenous mitomycin plus oral fluorouracil. We have assessed the efficacy of protein-bound polysaccharide (PSK) in addition to standard chemotherapy in patients who had undergone curative gastrectomy at 46 institutions in central Japan. 262 patients were randomly assigned standard treatment alone or with PSK. The minimum follow-up time was 5 years (range 5-7 years). PSK improved both the 5-year disease-free rate (70.7 vs 59.4% in standard treatment group, p = 0.047) and 5-year survival (73.0 vs 60.0%, p = 0.044). The two regimens had only slight toxic effects, consisting of nausea, leucopenia, and liver function impairment, and there were no significant differences between the groups. The treatments were clinically well tolerated and compliance was good. Addition of PSK to adjuvant chemotherapy with mitomycin and fluorouracil is beneficial as treatment after curative gastrectomy.

Adjuvants, Immunologic↗